Figure 7.

Schematic model showing the mechanism of lactate-mediated crosstalk between PA cells and tumor associated macrophages promoting tumor invasion. Overproduction of lactate in PA cells may contribute to malignant-like transformation at the early stage of PA formation. Lactate secreted by PA cells promote TAMs in the microenvironment towards M2 phenotype polarization via the mTORC2 and ERK1/2 pathways. In return, the CCL17 chemokine secreted by lactate-induced M2-like TAMs binds to its cognate receptor CCR4 on PA cells, thereby activating PA cells proliferation and invasion via the mTORC1 pathway.